The objectives of the proposed research are to identify the mechanism by which Aleutian disease virus produces a persistent infection in mink and to characterize the disease produced by the scrapie agent. When Aleutian disease virus is isolated from persistently infected mink, it will replicate in cell culture only at a temperature considerably less than the body temperature of mink. After cell culture passage, the virus can replicate at higher temperatures. We will assess the temperature-sensitivity of additional isolates of this virus. Culture-adapted virus which will replicate at the body temperature of mink will be inoculated into mink to find if temperature-sensitive virus is re-selected when the mink become persistently infected. Aleutian disease virus cannot be neutralized by mink antibody. The reason for the lack of neutralization will be studied using antiviral antibody prepared in other species and monodisperse virus separated from membrane fragments. The pathogenesis of Aleutian disease will also be studied in the closely related ferret. The causitive agent of scrapie appears not to be a conventional virus or a naked nucleic acid (viroid). An experiment to study the effect of scrapie virus on genetically differing mice will be conducted. BIBLIOGRAPHIC REFERENCES: Proter, D.D., Porter, H.G. and Larsen, A.E. Immunoglobulin class of Aleutian disease viral antibody. Fed. Proc. 36: 1268, 1977. Porter, D.D. and Larsen, A.E. Aleutian disease of mink: a persistent viral infection. Microbiology 1977, in press.